Endothelial Function in Hypertension

Abstract

Much attention has been focused on the role of nitric oxide in hypertension and cardiovascular disease. More recently, the role of superoxide anion and its interaction with nitric oxide has been investigated in this context. This review will concentrate on the role of superoxide in human and experimental hypertension, paying particular attention to the potential sources of superoxide within the vasculature and discussing some of the molecular mechanisms surrounding its production and dismutation. We discuss what is known about the human superoxide dismutase enzymes. We conclude that the balance between nitric oxide and superoxide is more important than the absolute levels of either alone.

Impact of the components of metabolic syndrome on oxidative stress and enzymatic antioxidant activity in essential hypertension

“…The increased OX in hypertensives has been attributed to the overactivity of mechanisms that increase ROS production which is mainly mediated by superoxide and hydroxyl radicals. 4,5 An alternative explanation for the high OX status observed in hypertensives, which does not exclude the former, is the impact of primary impairment of antioxidant enzymatic activity. Antioxidant enzymes constitute and represent an important part of the total antioxidant activity of aerobic cells and coordination of their functions results in the maintenance of ROS below critical levels compatible with cell viability and performance.…”

“…Hypertension is considered a state of oxidative stress (OX) that can contribute to the development of artherosclerosis 2 and other hypertension-induced organ damage. 3 Assessment of antioxidant activities and lipid peroxidation byproducts in hypertensives indicates an excessive amount of ROS and a reduction of antioxidant mechanism activity in blood, as well as in several other cellular systems, 4 including not only vascular wall cells, 5 but also those cells found in circulating blood. 6,7 Increased OX of hypertensive subjects improved with the antihypertensive treatment, and extending treatment over time increased the beneficial impact of treatment.…”

Gene Transfer of Endothelial NO Synthase and Manganese Superoxide Dismutase on Arterial Vascular Cell Adhesion Molecule-1 Expression and Superoxide Production in Deoxycorticosterone Acetate-Salt Hypertension

“…13,22 In an animal model of hypertension, Tummala et al 11 reported that Ang II stimulates VCAM-1 expression via the activation of oxidative signaling pathways involving the redox-sensitive transcription factor nuclear factor-B (NF-B) and the upregulation of genes downstream from NF-B, including VCAM-1. Other groups have shown that Ang II stimulates superoxide production via a membrane-bound NADPH oxidase.…”

“…24 -26 A major mechanism responsible for such an impairment is superoxide generated in the presence of the disease, which inactivates NO rapidly. 13,22 In various atherogenic models, the accumulation of T lymphocytes and monocytes at sites of vascular inflammation was shown to be VCAM-1 dependent. [2][3][4][5]27 Inflammatory mediators, including NF-B, are activated in part through the stimulation of superoxide production, resulting in attraction of macrophages, stimulation of foam cell formation, inflammation, and atherogenesis.…”

“…11 The elevated superoxide is present throughout the atherosclerotic vessel wall, 12 and a major source of superoxide is from the electron transport chain in mitochondrial respiration. 13 Two recent studies have indicated that there is also a substantial increase of vascular superoxide with reduced NO release in deoxycorticosterone acetate (DOCA)-salt hypertension, 14,15 a model well known for its suppressed plasma renin and angiotensin levels. 16 However, the level of vascular VCAM-1 expression has never been investigated in this model of hypertension.…”